NCT06252675

Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

A Multicenter Phase 2 Study of Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests the safety and effectiveness of glofitamab given in combination with pirtobrutinib in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Glofitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Obinutuzumab may also reduce the risk of immune-related conditions from treatment. Pirtobrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the protein that signals cancer cells to multiply. Giving glofitamab in combination with pirtobrutinib may be safe, tolerable and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

Detailed description

PRIMARY OBJECTIVES: I. To characterize the safety and tolerability of the combination of glofitamab and pirtobrutinib in the first six participants enrolled. II. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in participants with relapsed or refractory mantle cell lymphoma (MCL) as measured by complete response rate. SECONDARY OBJECTIVES: I. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in participants with relapsed or refractory MCL as measured by progression-free survival and overall survival. II. To characterize the magnitude and duration of anti-tumor activity by objective response rate and duration of response. III. To characterize the safety and tolerability of the combination of glofitamab and pirtobrutinib. IV. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in participants with relapsed or refractory MCL as measured by complete response without measurable disease (CRMRD-) rate. V. To evaluate the time-to-complete response without measurable residual disease (CRMRD-). VI. To evaluate the treatment-free interval among participants who discontinue treatment following CRMRD- status. EXPLORATORY OBJECTIVES: I. To explore associations between baseline tumor characteristics including genetic (e.g. mutations in BTK) and immune profiles (e.g. expression of co-inhibitory receptors and T cell phenotypes) and outcomes in participants administered the combination of glofitamab and pirtobrutinib. II. To explore the effects of the combination of glofitamab and pirtobrutinib on pharmacodynamic markers relating to drug mechanism (e.g. emergence of clones with mutations conferring resistance to the study combination). III. To estimate the quality of life of participants during therapy with glofitamab and pirtobrutinib. IV. To explore time-to-CRMRD- during therapy with glofitamab and pirtobrutinib. OUTLINE: Participants receive study treatments until the absence of disease progression or unacceptable toxicity. Participants may also have a bone marrow biopsy and aspiration at cycle 13 and plasma and blood samples collected throughout study for correlative research. Additionally, participants may undergo a tissue biopsy at relapse or progression. Participants are followed for 30 days after treatment discontinuation for safety. Participants who discontinue treatment due to complete response (CR) with undetectable MRD will complete in-person visits through the end of study visit, 94 weeks from start of treatment. Participants who discontinue treatment for any reason other than CR will be followed every 3 months for up to 94 weeks from start of treatment, until death, loss to follow up, study termination, or participant withdrawal.

Conditions

• Mantle Cell Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	Obinutuzumab	Given intravenously (IV)
BIOLOGICAL	Glofitamab	Given IV
DRUG	Pirtobrutinib	Given Orally (PO)
PROCEDURE	Tumor Imaging	Undergo regular care imaging/scans
PROCEDURE	Biospecimen Collection	Blood and tissue samples
DEVICE	ClonoSeq Assay	ClonoSEQ is an FDA-cleared, Clinical Laboratory Improvement Amendments of 1988 (CLIA)-validated measure used to determine minimal residual disease (MRD). This helps uncover how much, if any, cancer remains in your body during and after treatment.
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and aspiration.

Timeline

• Start date: 2024-06-11
• Primary completion: 2028-07-31
• Completion: 2028-07-31
• First posted: 2024-02-12
• Last updated: 2025-10-22

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study